Mosquito control measures have lowered malaria rates, but drug resistant strains are causing concern. More than 650,000 people die of malaria every year, mostly in developing countries. Thanks to measures prevent mosquito bites and the development of new drugs, mortality from malaria has decreased drastically over the last decade. One commonly used treatment is the drug artemisinin, derived from the plant Artemisia annua. Artemisinin is often used in combination with other agents, and this artemisinin combination therapy (ACT) is recommended as a first-line therapy for malaria caused by Plasmodium falciparum, the most dangerous malaria parasite. Artemisinin acts rapidly to destroy the parasite that causes malaria, but does not entirely eliminate the parasite. ACT combines the rapid-acting effects of artemisinins with longer acting agents to eliminate the parasite. This has reduced the burden of malaria in China and Sub-Saharan Africa.

In the last several years, resistance to artemisinin has posed a challenge in the fight against malaria. Resistant plasmodium strains have recently been reported in Cambodia, Thailand and parts of Myanmar. Resistance to chloroquine -- another drug against malaria -- also emerged in Southeast Asia and subsequently spread to Sub-Saharan Africa. There is concern that artemisinin resistance may follow a similar pattern. Containing resistance and preventing the spread to other regions of the world is paramount in the fight against malaria, but there is little information on the mechanisms that result in resistance. A paper published in Science last week reported chromosomal regions that may be involved in conferring resistance against artemisinin; however, the specific genes remain unknown. Determining what genes confer resistance is not only important for our understanding of the mechanisms of drug resistance; these genes may also serve as screening tools for rapid identification of resistant strains.

A researcher in a Maryland lab studies malaria parasites. The World Health Organization’s (WHO) Global Plan for Artemisinin Resistance Containment (GPARC) recommends a broad range of research activities to improve resistance containment. These include:

1) Laboratory research: This would be targeted at identifying the molecular mechanisms involved in resistance

2) Research and development (R&D): Aimed at developing new drugs and combination therapies

3) Applied and field research: Field-based studies of screening programs and mass drug administration programs

4) Operational research: Improving the effectiveness of the newest treatments and tools to reduce resistance in the field

5) Mathematical modeling: Measuring the potential impact of malaria treatment programs

While the burden of malaria is greatest in developing countries, these countries lag in terms of their ability to conduct research on malaria. One contributor to this lag is a lack of insufficient research funds. The Medicines for Malaria Venture (MMV), a non-profit organization that works on malaria reduction, estimates that an additional 10-15 million dollars a year are needed to fund artemisinin-resistance related laboratory research. Thus, developing countries and the international community must develop creative strategies to increase funding. One group involved in addressing this challenge is the WHO’s Consultative Expert Working Group on Research and Development (CEWG). This group was established based on the request of member states of WHO countries in order to address the lack of resources for R&D pertaining to diseases endemic in the developing world. As John-Arne Røttingen, chair of CEWG, explained, “Intellectual property rights and sales do not provide enough incentive to encourage investment on diseases that mainly affect people in developing countries.” In order to increase funding for various projects, the CEWG proposes placing taxes on harmful products such as tobacco and alcohol and allocating the revenue generated from these taxes to fund research. It also recommends dedicating portions of revenues generated from international indirect taxes to R&D efforts. In addition, the group has recommended a series of broader initiatives to enhance research in the developing world. These recommendations include:

1) Open knowledge innovation: Voluntary disclosure of information by private sector and academic institutions for the purpose of enhancing research. CEWG has proposed using prizes as a means of incentivizing open knowledge innovation.

2) Equitable licensing: Defining intellectual property rights pertaining to R&D through equitable licensing practices in order to ensure that research findings impact the greatest number of people.

3) Patent pools: Sharing of intellectual property rights pertaining to a medication or discovery.

Malaria parasites are spread by mosquitos. 4) Mandatory government commitments: Increasing government investments in R&D. As a preliminary recommendation, CEWG states that countries should invest 2 percent of their health funding on R&D efforts.

5) Pooling of funds: Bringing together multiple investors to invest in R&D funds. CEWG proposes that parts of these funds be used to increase capacity and improve technologies available for research in developing countries.

6) International binding convention on global health research: Establishing a binding convention based on the aforementioned principles. The purpose of this binding convention is to increase coordination for R&D. WHO would play a central role in coordination by bringing together various funders of research for open sharing of knowledge. It would also monitor and evaluate research activities. The CEWG states that this binding convention is not meant to replace current intellectual property rights but to augment them.

It is clear that a multitude of initiatives are needed to increase research on malaria in the developing world. Sustainable funding strategies that would allow ongoing R&D are instrumental. International donor organizations may help research funds grow by requiring a percentage of aid to be allocated to R&D efforts. Yet, even in the presence of funding, R&D in malaria-endemic regions cannot be driven by large financial incentives that often drive pharmaceutical innovation in developed countries. Ultimately, models are needed that separate large financial incentives from R&D efforts and promote medical innovation in countries that are endemic for malaria and similar diseases.

References:

Aung Pyae P, et al. Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study. The Lancet, doi:10.1016/S0140-6736(12)60484.

Dondorp AM, et al. Artemisinin Resistance in Plasmodium falciparum Malaria, New England Journal of Medicine, 365(12), Sept. 2011